Sunday, May 26, 2013

  •  "One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. It is also a recruiter of several chromatin remodeling enzymes such as methylases and acetylases. pRb belongs to the pocket protein family, whose members have a pocket for the functional binding of other proteins.[2][3] Should an oncogenic protein, such as those produced by cells infected by high-risk types of human papillomaviruses, bind and inactivate pRb, this can lead to cancer."


     Cyclin-dependent kinases (CDKs) play essential roles in cell proliferation and gene expression. Although distinct sets of CDKs work in cell division and transcription by RNA polymerase II (Pol II), they share a CDK-activating kinase (CAK), which is itself a CDK-Cdk7-in metazoans."FISHER ET AL


  • cholera toxin - increase cAMP levelsIn a cAMP-dependent pathway, the activated Gs alpha subunit binds to and activates an enzyme called adenylyl cyclase, which, in turn, catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP).[2] Increases in concentration of the second messenger cAMP may lead to the activation of
  • cyclic nucleotide-gated ion channels[3]
  • exchange proteins activated by cAMP (EPAC)[4] such as RAPGEF3
  • an enzyme called protein kinase A (PKA).[5]
The PKA enzyme is also known as cAMP-dependent enzyme because it gets activated only if cAMP is present. Once PKA is activated, it phosphorylates a number of other proteins including:[6]
  • enzymes that convert glycogen into glucose
  • enzymes that promote muscle contraction in the heart leading to an increase in heart rate
  • transcription factors, which regulate gene expression
Specificity of signaling between a GPCR and its ultimate molecular target through a cAMP-dependent pathway may be achieved through formation of a multiprotein complex that includes the GPCR, adenylyl cyclase, and the effector protein.[7]WIKIPEDIA

 (cyclin-dependent kinase 7 (CDK7) has essential roles in both the cell-division cycle and transcription, as a CDK-activating kinase (CAK) and as a component of the general transcription factor TFIIH,") FISHER

Cyclic AMP inhibits the proliferation of thyroid carcinoma cell lines through regulation of CDK4 phosphorylation.(Rocha)



Rb inactivation in cell cycle and cancer: the puzzle of highly regulated activating phosphorylation of CDK4 versus constitutively active CDK-activating kinase.(Paternot et al!)

LINKING  cyclic-AMP to Rb


activators of c-AMP

Paternot S, Bockstaele L,
  • forskolin - a diterpene natural product that activates adenylyl cyclase
  • caffeine and theophylline inhibit cAMP phosphodiesterase, which leads to an activation of G proteins that result in the activation of the cAMP pathway
  • bucladesine (dibutyryl cAMP, db cAMP) - also a phosphodiesterase inhibitor
  • pertussis toxin, which increase cAMP levels by inhibiting Gi to its GDP (inactive) form. This leads to an increase in adenylyl cyclase, therefore increasing cAMP levels, which can lead to an increase in insulin and therefore hypoglycemia (WIKIPEDIA)
drink coffee while on treatment with Melanoma ? or Rb driven disease?
take Theophylline for that matter!

Post a Comment